4,960 research outputs found
Improving Low-Resource Question Answering using Active Learning in Multiple Stages
Neural approaches have become very popular in the domain of Question
Answering, however they require a large amount of annotated data. Furthermore,
they often yield very good performance but only in the domain they were trained
on. In this work we propose a novel approach that combines data augmentation
via question-answer generation with Active Learning to improve performance in
low resource settings, where the target domains are diverse in terms of
difficulty and similarity to the source domain. We also investigate Active
Learning for question answering in different stages, overall reducing the
annotation effort of humans. For this purpose, we consider target domains in
realistic settings, with an extremely low amount of annotated samples but with
many unlabeled documents, which we assume can be obtained with little effort.
Additionally, we assume sufficient amount of labeled data from the source
domain is available. We perform extensive experiments to find the best setup
for incorporating domain experts. Our findings show that our novel approach,
where humans are incorporated as early as possible in the process, boosts
performance in the low-resource, domain-specific setting, allowing for
low-labeling-effort question answering systems in new, specialized domains.
They further demonstrate how human annotation affects the performance of QA
depending on the stage it is performed.Comment: 16 pages, 8 figure
Metformin Decreases the Incidence of Pancreatic Ductal Adenocarcinoma Promoted by Diet-induced Obesity in the Conditional KrasG12D Mouse Model.
Pancreatic ductal adenocarcinoma (PDAC) is a particularly deadly disease. Chronic conditions, including obesity and type-2 diabetes are risk factors, thus making PDAC amenable to preventive strategies. We aimed to characterize the chemo-preventive effects of metformin, a widely used anti-diabetic drug, on PDAC development using the KrasG12D mouse model subjected to a diet high in fats and calories (HFCD). LSL-KrasG12D/+;p48-Cre (KC) mice were given control diet (CD), HFCD, or HFCD with 5 mg/ml metformin in drinking water for 3 or 9 months. After 3 months, metformin prevented HFCD-induced weight gain, hepatic steatosis, depletion of intact acini, formation of advanced PanIN lesions, and stimulation of ERK and mTORC1 in pancreas. In addition to reversing hepatic and pancreatic histopathology, metformin normalized HFCD-induced hyperinsulinemia and hyperleptinemia among the 9-month cohort. Importantly, the HFCD-increased PDAC incidence was completely abrogated by metformin (p < 0.01). The obesogenic diet also induced a marked increase in the expression of TAZ in pancreas, an effect abrogated by metformin. In conclusion, administration of metformin improved the metabolic profile and eliminated the promoting effects of diet-induced obesity on PDAC formation in KC mice. Given the established safety profile of metformin, our findings have a strong translational potential for novel chemo-preventive strategies for PDAC
Duration of carriage of multidrug-resistant bacteria in dogs and cats in veterinary care and co-carriage with their owners.
Background
The emergence and spread of multidrug-resistant organisms (MDROs) represent a threat to human and animal health.
Objectives
To assess duration of carriage of MDROs in dogs and cats presented to veterinary clinics/hospitals in Switzerland. To estimate prevalence, duration of and risk factors for MDRO carriage in their owners and the occurrence of co-carriage in owner-pet pairs.
Methods
Prospective, longitudinal, observational study. Nasal swabs and fecal samples were collected from 50 owners of dogs and cats presented to 3 large veterinary hospitals, 1 medium-sized clinic and 1 practice. If pet or owner tested positive for a MDRO, follow-up samples were collected for up to 8 months. Methicillin-resistant (MR) Staphylococcus aureus, MR S. pseudintermedius, MR coagulase-negative staphylococci (MRCoNS), MR Macrococcus spp., cephalosporinase- and carbapenemase-producing (CP) Enterobacterales were isolated and further characterized by MALDI-TOF MS, microdilution, β-lactam resistance gene detection, REP/ERIC-PCR, multilocus sequence typing or whole-genome sequencing. Risk factors for MDRO carriage in owners were explored based on questionnaire-derived data.
Results
Five out of 50 owners carried 3rd generation cephalosporin-resistant Enterobacterales (3GC-R-Ent.), and 5/50 MRCoNS. In 3 dogs and 4 cats carriage of 3GC-R-Ent. persisted for up to 136 days after discharge (median 99 days, IQR 83 days, range 36-136 days), in two cats isolates were carbapenem-resistant. Owner-pet co-carriage was not observed. No specific risk factors for MDRO carriage in owners were identified.
Conclusions
After discharge from veterinary care, dogs and cats may carry 3GC-R-Ent. for prolonged time periods. Carriage of MDROs was common in owners, but pet-owner co-carriage of the same MDRO was not observed
Sprouty2 mediated tuning of signalling is essential for somite myogenesis
Background: Negative regulators of signal transduction cascades play critical roles in controlling different aspects of normal embryonic development. Sprouty2 (Spry2) negatively regulates receptor tyrosine kinases (RTK) and FGF signalling and is important in differentiation, cell migration and proliferation. In vertebrate embryos, Spry2 is expressed in paraxial mesoderm and in forming somites. Expression is maintained in the myotome until late stages of somite differentiation. However, its role and mode of action during somite myogenesis is still unclear. Results: Here, we analysed chick Spry2 expression and showed that it overlaps with that of myogenic regulatory factors MyoD and Mgn. Targeted mis-expression of Spry2 led to inhibition of myogenesis, whilst its C-terminal domain led to an increased number of myogenic cells by stimulating cell proliferation. Conclusions: Spry2 is expressed in somite myotomes and its expression overlaps with myogenic regulatory factors. Overexpression and dominant-negative interference showed that Spry2 plays a crucial role in regulating chick myogenesis by fine tuning of FGF signaling through a negative feedback loop. We also propose that mir-23, mir-27 and mir-128 could be part of the negative feedback loop mechanism. Our analysis is the first to shed some light on in vivo Spry2 function during chick somite myogenesis
The chicken talpid3 gene encodes a novel protein that is essential for hedgehog signaling
Talpid(3) is a classical chicken mutant with abnormal limb patterning and malformations in other regions of the embryo known to depend on Hedgehog signaling. We combined the ease of manipulating chicken embryos with emerging knowledge of the chicken genome to reveal directly the basis of defective Hedgehog signal transduction in talpid(3) embryos and to identify the talpid(3) gene. We show in several regions of the embryo that the talpid(3) phenotype is completely ligand independent and demonstrate for the first time that talpid(3) is absolutely required for the function of both Gli repressor and activator in the intracellular Hedgehog pathway. We map the talpid(3) locus to chromosome 5 and find a frameshift mutation in a KIAA0586 ortholog (ENSGALG00000012025), a gene not previously attributed with any known function. We show a direct causal link between KIAA0586 and the mutant phenotype by rescue experiments. KIAA0586 encodes a novel protein, apparently specific to vertebrates, that localizes to the cytoplasm. We show that Gli3 processing is abnormal in talpid(3) mutant cells but that Gli3 can still translocate to the nucleus. These results suggest that the talpid(3) protein operates in the cytoplasm to regulate the activity of both Gli repressor and activator proteins
Whole-body imaging of the musculoskeletal system: the value of MR imaging
In clinical practice various modalities are used for whole-body imaging of the musculoskeletal system, including radiography, bone scintigraphy, computed tomography, magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT). Multislice CT is far more sensitive than radiographs in the assessment of trabecular and cortical bone destruction and allows for evaluation of fracture risk. The introduction of combined PET-CT scanners has markedly increased diagnostic accuracy for the detection of skeletal metastases compared with PET alone. The unique soft-tissue contrast of MRI enables for precise assessment of bone marrow infiltration and adjacent soft tissue structures so that alterations within the bone marrow may be detected before osseous destruction becomes apparent in CT or metabolic changes occur on bone scintigraphy or PET scan. Improvements in hard- and software, including parallel image acquisition acceleration, have made high resolution whole-body MRI clinically feasible. Whole-body MRI has successfully been applied for bone marrow screening of metastasis and systemic primary bone malignancies, like multiple myeloma. Furthermore, it has recently been proposed for the assessment of systemic bone diseases predisposing for malignancy (e.g., multiple cartilaginous exostoses) and muscle disease (e.g., muscle dystrophy). The following article gives an overview on state-of-the-art whole-body imaging of the musculoskeletal system and highlights present and potential future applications, especially in the field of whole-body MRI
Multiplicities of charged pions and unidentified charged hadrons from deep-inelastic scattering of muons off an isoscalar target
Multiplicities of charged pions and unidentified hadrons produced in
deep-inelastic scattering were measured in bins of the Bjorken scaling variable
, the relative virtual-photon energy and the relative hadron energy .
Data were obtained by the COMPASS Collaboration using a 160 GeV muon beam and
an isoscalar target (LiD). They cover the kinematic domain in the photon
virtuality > 1(GeV/c, , and . In addition, a leading-order pQCD analysis was performed using the
pion multiplicity results to extract quark fragmentation functions
Search for CP Violation in the Decay Z -> b (b bar) g
About three million hadronic decays of the Z collected by ALEPH in the years
1991-1994 are used to search for anomalous CP violation beyond the Standard
Model in the decay Z -> b \bar{b} g. The study is performed by analyzing
angular correlations between the two quarks and the gluon in three-jet events
and by measuring the differential two-jet rate. No signal of CP violation is
found. For the combinations of anomalous CP violating couplings, and , limits of \hat{h}_b < 0.59h^{\ast}_{b} < 3.02$ are given at 95\% CL.Comment: 8 pages, 1 postscript figure, uses here.sty, epsfig.st
Search for Third Generation Vector Leptoquarks in p anti-p Collisions at sqrt(s) = 1.96 TeV
We describe a search for a third generation vector leptoquark (VLQ3) that
decays to a b quark and tau lepton using the CDF II detector and 322 pb^(-1) of
integrated luminosity from the Fermilab Tevatron. Vector leptoquarks have been
proposed in many extensions of the standard model (SM). Observing a number of
events in agreement with SM expectations, assuming Yang-Mills (minimal)
couplings, we obtain the most stringent upper limit on the VLQ3 pair production
cross section of 344 fb (493 fb) and lower limit on the VLQ3 mass of 317
GeV/c^2 (251 GeV/c^2) at 95% C.L.Comment: 7 pages, 2 figures, submitted to PR
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition
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